Can Botox Take Away Frown and Depression?

Action Points

Note that this small randomized trial demonstrated an association between Botox injections (to paralyze "frown" muscles) and improved depression symptomatology.

Be aware that adequate blinding would have been very hard to maintain in a study such as this.

Botox injections to disable the facial muscles responsible for frowning were effective in relieving clinical depression in a randomized, placebo-controlled trial, researchers said.

Among 33 patients meeting DSM-IV criteria for major depression who were assigned to receive Botox (onabotulinumtoxinA) injections, 17 (52%) showed decreases of at least 50% from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) scores 6 weeks after treatment, compared with six of 41 (15%) injected with saline (P<0.001), according to Eric Finzi, MD, PhD, of the Chevy Chase Cosmetic Center in Chevy Chase, Md., and Norman E. Rosenthal, MD, of Georgetown University in Washington, D.C.

Clinical remission, defined as a MADRS score of 10 or less at final evaluation, was achieved by 27% of the Botox group versus 7% of the placebo group (P=0.03), Finzi and Rosenthal reported online in the Journal of Psychiatric Research.

The results confirm and expand on a 30-patient German trial published in the same journal in 2012, the researchers indicated. In that trial, patients with both observable frowns and persistent depression despite conventional treatments who received Botox injections in the glabellar region showed significantly greater reductions in Hamilton Depression Rating Scale scores than a placebo group.

Finzi and Rosenthal said the current study bolsters these findings not only by having more patients, but also because the clinical mix of patients was broader and the results included a clear advantage in symptom remission, which was not the case in the German study.

Overall, the two studies add to a growing body of evidence that facial expressions may affect mood. Past studies have found, for example, that forcing smiles can lead to subjective mood improvements, and now it appears that simply incapacitating the muscles responsible for producing unhappy expressions can have a similar effect.

In the current study, Finzi and Rosenthal recruited a total of 85 patients with major depression as diagnosed from a standard clinical interview. Inclusion criteria also included a MADRS score of at least 26 at screening as well as a Clinical Global Impression-Severity (CGI-S) score of at least 4. Patients with significant comorbid psychiatric conditions were excluded, as were those considered at high risk for suicide and those failing at least three prior antidepressant regimens in different classes.

Of the 85 randomized, eight in the Botox group and three in the placebo group were dropped from the analysis. Reasons included protocol violations (starting a new antidepressant drug therapy), withdrawal of consent, or loss to follow-up.

Injections were delivered at five locations in the corrugator and procerus muscles between the eyebrows, roughly defining a letter V. Total doses were 29 units for women and 40 units for men.

At week six after injection, 21 of 33 patients receiving Botox were rated as "much improved" on the CGI-S compared with eight of 41 in the placebo group (P=0.0001).

In addition, "a significant mixed model interaction was observed between the drug and depression scores over time" in scores on the Beck Depression Inventory II, the researchers wrote (analysis of variance F (2,139)=11.3, P<0.0001).

Finzi and Rosenthal also had two dermatologists analyze the appearance of frowns in patients' faces, based on photographs provided by the study team, rating them with a "frown score" before and after treatment. In just under two-thirds of cases, the presence or absence of significant changes in frown score corresponded to a clinical depression response or nonresponse -- a nonsignificant trend, the researchers noted.

In fact, they added, five of 13 patients in the Botox group whose baseline photos at rest showed "no discernible frown" still obtained a complete remission of depression.

Because the Botox effect may be detected by patients, blinding in the trial could have been partially compromised. To see if this had an effect on results, Finzi and Rosenthal asked patients to guess their assignments at the end of the study. About half in both groups guessed correctly, about one-third guessed wrongly, and the remainder did not venture a guess.

Analyses of these data against MADRS scores indicated that the effects on depression were the same in those guessing correctly versus those who guessed incorrectly.

The investigators, in their conclusions, identified several potential advantages of Botox as a depression treatment:

Improved compliance

Cost-effective (although the researchers did not evaluate it numerically)

Few drug interactions

Well-documented safety

However, Finzi and Rosenthal also noted several limitations of the study. Because more than 90% of participants were women, conclusions about the treatment's effectiveness in men are premature. The study's 6-week duration meant the antidepressant effect's durability remains in question. And, a mean of 9 days elapsed between screening and treatment, during which participants' depression may have changed.

Another feature of the study that might be considered a limitation was the placebo response rate, which was considerably lower than normally seen in antidepressant treatment trials.

The researchers had no firm explanation, but they offered several possibilities: participants were not paid for participation in the study, they had only about half the number of clinic visits typical in a drug trial, and/or the compromised blinding may have diminished the placebo response.

The study was funded by the Chevy Chase Cosmetic Center, of which Finzi is sole owner. Finzi has received a patent for treating depression with botulinum toxin. Rosenthal declared he had no relevant financial interests.

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